Evidence map›Paper›PMID 38269648›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Rational Identification of Novel Antibody-Drug Conjugate with High Bystander Killing Effect against Heterogeneous Tumors.

Yu Guo, Zheyuan Shen, Wenbin Zhao, Jialiang Lu, Yi Song, Liteng Shen, Yang Lu, Mingfei Wu, Qiuqiu Shi, Weihao Zhuang and 6 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Yu GuoHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Zheyuan ShenHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Wenbin ZhaoInnovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310018, P. R. China.
Jialiang LuHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Yi SongHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Liteng ShenHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Yang LuHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Mingfei WuHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Qiuqiu ShiHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Weihao ZhuangHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Yueping QiuThe Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, 310022, P. R. China.
Jianpeng ShengDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310002, P. R. China.
Zhan ZhouInnovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310018, P. R. China.
Luo FangThe Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, 310022, P. R. China.
Jinxin CheHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.
Xiaowu DongHangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.ORCID 0000-0002-2178-4372

Funding

Key R&D Program of Zhejiang Province 2023C03111National Natural Science Foundation of China 81973172National Natural Science Foundation of China 82003579National Natural Science Foundation of China 82173660Natural Science Foundation of Zhejiang Province LQ21H300005Natural Science Foundation of Zhejiang Province LR21H300003
6 · The paper itself

Abstract

Bystander-killing payloads can significantly overcome the tumor heterogeneity issue and enhance the clinical potential of antibody-drug conjugates (ADC), but the rational design and identification of effective bystander warheads constrain the broader implementation of this strategy. Here, graph attention networks (GAT) are constructed for a rational bystander killing scoring model and ADC construction workflow for the first time. To generate efficient bystander-killing payloads, this model is utilized for score-directed exatecan derivatives design. Among them, Ed9, the most potent payload with satisfactory permeability and bioactivity, is further used to construct ADC. Through linker optimization and conjugation, novel ADCs are constructed that perform excellent anti-tumor efficacy and bystander-killing effect in vivo and in vitro. The optimal conjugate T-VEd9 exhibited therapeutic efficacy superior to DS-8201 against heterogeneous tumors. These results demonstrate that the effective scoring approach can pave the way for the discovery of novel ADC with promising bystander payloads to combat tumor heterogeneity.

Indexed as

ImmunoconjugatesCell Line, TumorImmunoconjugatesantibody‐drug conjugatesbystander‐killing effectcamptothecin derivativesrational designtumor heterogeneity

Identifiers

PMID38269648
PMCPMC10987111

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.